More than 80% of children with stage IV neuroblastoma are not cured by standard therapies. There are multiple reasons for this failure: large tumor load, drug resistance and treatment toxicities. Pilot phase II studies using immunotherapy or differentiation inducers have shown limited success in shrinking bulky tumor. Adjuvant studies in patients with minimal microscopic disease are difficult to interpret because of the lack of randomized control arms. Since each randomized trial requires a large number of patients and the testing of only one treatment variable, it becomes a daunting task for a relatively rare cancer like neuroblastoma. The N6 protocol has been designed to test a novel combination therapy and to examine the validity of new probes to measure treatment efficacy. It intends to optimize the sequential delivery of (1) dose-intensive induction therapy, followed by (2) monoclonal antibody (MoAb) immunotherapy. The response to induction therapy is assessed prior to consolidation with MoAb. The anti-tumor effect of MoAb in the setting of microscopic disease is evaluated by immunoscintigraphy and by sensitive immunological plus molecular probes. In addition, we will utilize regression models which correlate measures of treatment efficacy with dose intensities of individual drugs, to predict the response rate, survival and progression-free survival durations achievable with N6. We hypothesize that while the actual response rate of the induction therapy will be no better than predicted, the median survival and PFS durations among patients will be significantly longer because of the immunotherapy. Preliminary analysis of our pilot N6 study has demonstrated feasibility, and the treatment results have agreed with our projections. We are requesting funding to continue patient accrual and to explore the immune mechanisms of host antitumor effects. Using monoclonal anti-idiotypic antibodies (Ab2), we will investigate the presence of (1) anti-anti- idiotypic antibodies (Ab3) and (2) specific cytotoxic T-lymphocytes in patients treated with MoAb. This clinical trial will test the validity of both a new treatment approach and the novel methods to measure efficacy -- critical elements in the development of new modalities for curing rare diseases. Since GD2 is found on a variety of human tumors, these results may have therapeutic implications for other equally refractory cancers.